The transition from progenitor to differentiated cells is critical for successful organogenesis; subtle alterations in this process can lead to developmental disorders. The anterior heart field (AHF) encompasses a niche in which cardiac progenitors maintain their multipotent and undifferentiated nature by signals from the surrounding tissues, which thus far have been poorly defined. Using systems biology approaches and perturbations of signaling molecules in chick embryos, we revealed a tight crosstalk between the bone morphogenic protein (BMP) and fibroblast growth factor (FGF) signaling pathways within the AHF: BMP4 promotes myofibrillar gene expression and cardiomyocyte contractions, by blocking FGF signaling. Furthermore, inhibition of the FGF-ERK pathway is both sufficient and necessary for these processes, suggesting that FGF signaling blocks premature differentiation of cardiac progenitors in the AHF. Investigating the molecular mechanisms downstream to BMP signaling revealed that BMP4 induced a set of neural crest-related genes; including MSX1, which was sufficient to induce cardiomyocyte differentiation. We suggest that BMP and FGF signaling pathways act via inter- and intra-regulatory loops in multiple tissues, to coordinate the balance between proliferation and differentiation of cardiac progenitors.
BMP-mediated inhibition of FGF signaling promotes cardiomyocyte differentiation of anterior heart field progenitors.
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View SamplesAnalysis of estrogen receptor (ER)-positive MCF7 cell total RNA expression and polysome-assiciated RNA expression following treatment with estradiol (E2) and vehicle (etoh).
Estrogen coordinates translation and transcription, revealing a role for NRSF in human breast cancer cells.
Cell line
View SamplesRNAseq analysis of cell lines with ADAR1-p150 and ADAR1-p110 knock-outs and primary human tissue samples (from GSE57353 and GSE99392 data sets) to identify sites of ADAR1 editing Overall design: 12 samples: 3 cell lines (HeLa, HeLa-p150KO, HeLa-ADAR1KO) with four conditions each (no treatment, MeV-vac2(GFP)-infected, MeV-CKO(GFP)-infected, IFNA/D-treated). One biological replicate per sample. In addition, raw data files of 9 samples from series GSE57353 and GSE99392 were re-analyzed using the same data processing pipeline.
Extensive editing of cellular and viral double-stranded RNA structures accounts for innate immunity suppression and the proviral activity of ADAR1p150.
Cell line, Subject
View SamplesU2AF65 is an essential splicing factor involved in the 3'splice site recognition dureing the first steps of spliceosome assembly. In addition, this protein has nucleocytoplasmic shuttling activity and the Drosophila homologue has been implicated in mRNA export.
Genome-wide identification of functionally distinct subsets of cellular mRNAs associated with two nucleocytoplasmic-shuttling mammalian splicing factors.
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View SamplesPTB is multifunctional RNA binding protein reported to be involved in splicing, 3' -end processing, stability and translational regulation.
Genome-wide identification of functionally distinct subsets of cellular mRNAs associated with two nucleocytoplasmic-shuttling mammalian splicing factors.
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View SamplesDisruption of peripheral circadian rhyme pathways dominantly leads to metabolic disorders. Studies on circadian rhythm proteins in the heart indicated a role for Clock or Per2 in cardiac metabolism. In fact, Per2-/- mice have larger infarct sizes with a deficient lactate production during myocardial ischemia. To test the hypothesis that cardiac Per2 represents an important regulator of cardiac metabolism during myocardial ischemia, we performed lactate measurements during reperfusion in Per1-/-, Per2-/- or wildtype mice followed by gene array studies using various ischemia-reperfusion protocols comparing wildtype and Per2-/- mice. Lactate measurements in whole blood confirmed a dominant role of Per2 for lactate production during myocardial ischemia. Surprisingly, high-throughput gene array analysis of eight different conditions on one 24-microarray plate revealed dominantly lipid metabolism as differentially regulated pathway in wildtype mice when compared to Per2-/-. In all treatment groups, the enzyme enoyl-CoA hydratase, which is essential in fatty acid beta-oxidation, was regulated in wildtype animals only. Studies using nuclear magnet resonance imaging (NMRI) confirmed altered fatty acid populations with higher mono-unsaturated fatty acid levels in hearts from Per2-/- mice. Unexpectedly, studies on gene regulation during reperfusion revealed solely pro inflammatory genes as differentially regulated 'Per2-genes'. Subsequent studies on inflammatory markers showed increasing IL6 or TNFa levels during reperfusion in Per2-/- mice. In summary, these studies reveal a novel role of cardiac Per2 for fatty acid metabolism or inflammation during myocardial ischemia and reperfusion.
Cardiac Per2 functions as novel link between fatty acid metabolism and myocardial inflammation during ischemia and reperfusion injury of the heart.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Expression of three topologically distinct membrane proteins elicits unique stress response pathways in the yeast Saccharomyces cerevisiae.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
The blood transcriptional signature of chronic hepatitis C virus is consistent with an ongoing interferon-mediated antiviral response.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
MicroRNA profiling in mucosal biopsies of eosinophilic esophagitis patients pre and post treatment with steroids and relationship with mRNA targets.
Specimen part, Disease
View SamplesThis study characterizes the effects of chronic Hepatitis C virus (HCV) infection on gene expression by analyzing blood samples from 10 treatment-naive HCV patients and 6 healthy volunteers.
The blood transcriptional signature of chronic hepatitis C virus is consistent with an ongoing interferon-mediated antiviral response.
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